Alternative Radionuclide Production with a Cyclotron

By IAEA

Cyclotrons are currently used for the preparation of a wide variety of radionuclides that have applications in single photon emission computed tomography (SPECT) and positron emission tomography (PET). Consequently, there is high demand from IAEA Member States for support in the area of radiopharmaceutical production using cyclotron produced radioisotopes. This publication describes the potential radionuclide production routes using cyclotrons in different energy ranges and provides methods for the development of targets and provides details of the chemistry for the separation of radionuclides from target materials. The readership of this publication includes scientists, operators interested in putting this technology into practice, technologists already working with cyclotrons who wish to enhance the utility of existing machines, and managers in the process of setting up radionuclide facilities in their countries. Students working towards higher level degrees in related fields may also benefit from this publication.

• Language: English
• Publisher: International Atomic Energy Agency
• Release date: Oct 1, 2021
• ISBN: 9789201032218

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ALTERNATIVE RADIONUCLIDE

PRODUCTION

WITH A CYCLOTRON

IAEA RADIOISOTOPES AND RADIOPHARMACEUTICALS REPORTS No. 4

ALTERNATIVE RADIONUCLIDE

PRODUCTION

WITH A CYCLOTRON

INTERNATIONAL ATOMIC ENERGY AGENCY

VIENNA, 2021

COPYRIGHT NOTICE

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© IAEA, 2021

Printed by the IAEA in Austria

September 2021

STI/PUB/1937

IAEA Library Cataloguing in Publication Data

Names: International Atomic Energy Agency.

Title: Alternative radionuclide production with a cyclotron / International Atomic Energy Agency.

Description: Vienna : International Atomic Energy Agency, 2021. | Series: IAEA radioisotopes and radiopharmaceuticals reports, ISSN 2413–9556 ; no. 4 | Includes bibliographical references.

Identifiers: IAEAL 21-01422 | ISBN 978-92-0-103021-4 (paperback : alk. paper) | ISBN 978-92-0-103121-1 (pdf) | ISBN 978-92-0-103221-8 (epub)

Subjects: LCSH: Radioisotopes. | Cyclotrons. | Radiopharmaceuticals. | Nuclear medicine.

Classification: UDC 621.039.574.5 | STI/PUB/1937

FOREWORD

Cyclotrons are currently used for the preparation of a wide variety of radionuclides that have applications in single photon emission computed tomography (SPECT) and positron emission tomography (PET). Consequently, there is high Member State demand for support in the area of radiopharmaceutical production using cyclotron produced radioisotopes. There are now more than 1300 cyclotron facilities worldwide, and that number is growing every year, with the highest rate of growth occurring in developing countries.

The IAEA has carried out several projects to support radionuclide production using cyclotrons. To help Member States build expertise in the field of medical isotope production, it was decided to produce a technical publication covering the production of alternative radionuclides (other than the well established PET radionuclides) with cyclotrons. The primary aim was to demonstrate the significant potential for the development of new radionuclides at existing facilities with low and medium energy cyclotrons and to help operators and decision makers in planning upgrades of or building new cyclotron facilities.

Work on this publication was initiated during a consultants’ meeting held from 12 to 16 November 2018 at the IAEA Headquarters in Vienna, with contributions from dedicated experts in the fields of cyclotron utilization, radiochemical processing, isotope production and cyclotron based radiopharmaceutical preparation for clinical investigations. The publication is intended to provide information on practical production methods for cyclotron based radionuclides, with optimized purification techniques to obtain high specific activity and chemical purity for use in the medical-scale labelling of molecules.

This publication briefly describes the potential radionuclide production routes using cyclotrons in different energy ranges; methods for the development of targets; and the chemistry for the separation of radionuclides from target materials for the production of these radionuclides. The target readership of this publication includes scientists, operators interested in putting this technology into practice, technologists already working with cyclotrons who wish to enhance the utility of existing machines, and managers in the process of setting up radionuclide facilities in their countries. Students working towards higher level degrees in related fields may also benefit from this publication.

The IAEA wishes to thank all the participating consultants and contributors to this publication for their valuable input, and J.S. Vera Araujo for editorial support. The IAEA officer responsible for this publication was A. Jalilian of the Division of Physical and Chemical Sciences.

EDITORIAL NOTE

This publication has been edited by the editorial staff of the IAEA to the extent considered necessary for the reader’s assistance. It does not address questions of responsibility, legal or otherwise, for acts or omissions on the part of any person.

Although great care has been taken to maintain the accuracy of information contained in this publication, neither the IAEA nor its Member States assume any responsibility for consequences which may arise from its use.

Guidance provided here, describing good practices, represents expert opinion but does not constitute recommendations made on the basis of a consensus of Member States.

The use of particular designations of countries or territories does not imply any judgement by the publisher, the IAEA, as to the legal status of such countries or territories, of their authorities and institutions or of the delimitation of their boundaries.

The mention of names of specific companies or products (whether or not indicated as registered) does not imply any intention to infringe proprietary rights, nor should it be construed as an endorsement or recommendation on the part of the IAEA.

The IAEA has no responsibility for the persistence or accuracy of URLs for external or third party Internet web sites referred to in this book and does not guarantee that any content on such web sites is, or will remain, accurate or appropriate.

The authoritative version of this publication is the hard copy issued at the same time and available as pdf on www.iaea.org/publications. To create this version for e-readers, certain changes have been made, including a the movement of some figures and tables.

CONTENTS

1. INTRODUCTION

1.1. Background

1.2. Objective

1.3. Scope

1.4. Structure

2. CYCLOTRON PARAMETERS

2.1. General considerations

2.2. Positive versus negative ion cyclotrons

2.3. Cyclotron facilities

2.4. Cyclotron database

3. CYCLOTRON TARGETRY

3.1. General considerations

3.2. Target types

4. CYCLOTRON BASED ALTERNATIVE RADIONUCLIDE PRODUCTION

4.1. Overview

4.2. Actinium-225

4.3. Antimony

4.4. Arsenic

4.5. Astatine-211

4.6. Bismuth-213

4.7. Bromine

4.8. Calcium-47

4.9. Cobalt

4.10. Copper

4.11. Erbium-165

4.12. Gallium

4.13. Germanium-68

4.14. Indium

4.15. Iodine

4.16. Iron-52

4.17. Manganese-52g

4.18. Molybdenum-99

4.19. Niobium-90g

4.20. Paladium-103

4.21. Platinum-191

4.22. Rhenium-186g

4.23. Scandium

4.24. Strontium-82

4.25. Technetium

4.26. Terbium-149

4.27. Thallium-201

4.28. Tin-117m

4.29. Titanium

4.30. Yttrium-86

4.31. Zinc

4.32. Zirconium-89g

5. CONCLUSION

REFERENCES

ABBREVIATIONS

CONTRIBUTORS TO DRAFTING AND REVIEW

1. INTRODUCTION

1.1. Background

Radionuclides produced with cyclotrons and their corresponding radiopharmaceuticals have demonstrated their enormous value in basic medical research, disease diagnosis and radiotherapy treatment. There are more than 1300 cyclotron facilities worldwide, and that number is growing every year. Cyclotrons come with different energy ranges and associated equipment, such as target ports with or without beamlines, depending on the functions for which they are intended. Most of these cyclotrons are not running at full capacity and production is often limited to one or two positron emission tomography (PET) tracers that are in routine clinical use. Beam time in many cyclotron facilities is underutilized, with only about 15 to 20 hours per week being devoted to radionuclide production. If this time could be utilized to enable research and development (R&D) activities and to produce other radionuclides that have demonstrated or potential clinical applications, the nuclear medicine and research programmes of the Member States would clearly benefit. Depending on the energy and type of the accelerated particle, cyclotrons could be ideal for producing the standard PET and single photon emission computed tomography (SPECT) radioisotopes, but could also be well suited to the production of several non-standard positron or single photon emitting radionuclides. The development of such radionuclides involves the study and optimization of aspects such as nuclear data, proper and cost effective targetry, chemical processing, automation and quality control. In order to produce a viable product with high labelling efficiency, both the radionuclidic purity and the specific radioactivity of the product need to be maintained at a very high level.

The development of new radiopharmaceuticals that can be routinely used for diagnosis or for evaluation of radiotherapy would provide valuable additions to the arsenal available to nuclear medicine physicians. However, there are several other limiting factors in the production and use of new radiopharmaceuticals. The time necessary for conversion from